5.1 What are the mechanisms of resistance to triclosan?

At high concentrations,
triclosan works by
interfering with the outer membrane that protects
bacteria, making it
permeable so that triclosan can penetrate it and kill the
microorganism. At
lower concentrations, triclosan attacks several targets. For
instance, it slows down drastically several important
biochemical reactions inside the bacteria.

Some bacteria have an
innate resistance to
triclosan,
possibly because their outer membrane does not let it through.
Bacteria can also become
resistant to
biocides using a
variety of methods that lower the concentration of
biocide inside the
bacteria. For instance, some bacteria have mutated so that
triclosan does not disrupt their vital biochemical reactions, or
they have found ways of bypassing the steps in these reactions
that are affected by triclosan. Other bacteria have developed
systems that “pump out” any substances that are harmful to them,
such as triclosan. In principle, some of these defence
mechanisms can be passed not only from one generation of
bacteria to the next, but also from one
bacterium to
another.

Different mechanisms may also work in conjunction and
together, have a greater effect than each one has separately.
For instance, some highly
resistantbacteria have both: a
modified outer membrane that does not let
triclosan through
easily, and ways of expelling any of the
biocide that manages to
get inside the cell.

Biofilms require a
special mention. Bacteria
are rarely found as single individuals. Instead, huge numbers
join together and attach themselves to surfaces forming a
biofilm. These bacterial
biofilms have a wide repertoire of defence mechanisms and are
much more resistant to
antimicrobials
than are isolated bacteria.
There is very little research in this field but there is some
evidence that biocides
could be ineffective against biofilms made of resistant
bacteria. On a positive note, using
triclosan followed by
an antibiotic could be
effective against bacterial biofilms. This would be extremely
beneficial given the serious problems that biofilms pose in
hospitals and other medical centres.
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5.2 Could exposure to triclosan lead to cross-resistance to antibiotics?

When bacteria are exposed
to triclosan, some strains
become resistant to it by
mutating or by activating
resistance genes. Some
of these genes are also
involved in
cross-resistance and
multi-resistance to different types of
antibiotics and
biocides so there
is a concern that exposing bacteria to low
concentrations of
triclosan could lead to the emergence of highly resistant
bacteria that would be very difficult or virtually impossible to
eradicate. However, a study from 2004 found that treating
bacteria with low concentrations of triclosan does not generally
lead to drug-resistance, and any resistance cannot be
transferred from one bacterialspecies to another.

Several laboratory studies have found that
bacteria which are
resistant to a
biocide are also
resistant to other types of
antimicrobials.
However, to date there is no evidence of a similar link in real
situations outside the laboratory. The results vary with the
concentration of biocide used and also with the
species of
microorganism
investigated. Some bacteria that are treated with relatively low
concentrations of
triclosan become
less susceptible to
antibiotics. However, other
types of bacteria are unaffected and, in the case of E. coli,
triclosan-resistant bacteria were more easily treated with an
antibiotic than the
original or unexposed strain.
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5.3 Has bacterial resistance to triclosan been observed in the environment?

Triclosan is the most
studied of all biocides but
most of the research has been done on laboratory samples and at
concentrations too
low to be of relevance to real working situations. Despite these
caveats, we can draw some useful conclusions.

A study from 2006 on
bacteria collected from
human saliva and a second one from 2004 on bacteria found in
teeth concluded that repeated exposures to
triclosan did not
systematically produce high level triclosan
resistance in all
bacteria. A relatively small number of strains did become harder
to treat to triclosan but many others didn’t. What is more, the
increased resistance was limited to triclosan so even
triclosan-resistant
strains could still be killed by other
biocides and by
antibiotics.

A study from 2003 tested samples of
bacteria collected in
consumers’ homes and found that households that used
antibacterial products had fewer harmful bacteria than those who
didn’t. In both cases, the researchers did not find any evidence
of cross resistance, and
strains of bacteria that were
resistant to
antibiotics were
still susceptible to antibacterial products. Users of
antibacterial handwash did not harbour any more resistant
strains of bacteria in their hands compared to non-users.

Triclosan is sometimes
added to toothpaste to control plaque and improve the health of
gums. These products are generally effective and there is no
evidence that using triclosan-containing toothpaste leads to
increased resistance or to
cross-resistance.

With respect to
microorganisms in the
environment, whether or not a strain of
bacteria becomes
resistant to
triclosan depends
largely on the concentration of the substance that reaches it
and this is by no means simple to measure. Triclosan attaches
itself to solid particles and may
bioaccumulate, posing a
concern for aquatic organisms; but on the other hand, is
degraded by ozone,
chlorine, sunlight and by
micro-organisms. Some of the
concentrations of
triclosan measured in the wastewater, sediments and sludge from
wastewater treatment plants are high enough to affect
microorganisms but we do not know how much of this triclosan is
actually taken up by bacteria. In addition to triclosan, there
are other biocides and
antibiotics present
in the environment and it is difficult to assess the effect of
triclosan alone, or to understand how these different
antimicrobials
work when combined.
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5.4 How can bacterial resistance be determined?

In most cases,
resistance has been
determined by measuring the minimum concentration of
biocide that will
stop bacterial growth
(MIC). Whether or not a strain of
bacteria is found to be
resistant by this
measure is largely irrelevant because the
concentrations of
triclosan used in
practice are considerable larger than these MIC values, and are
sufficient to kill all the bacteria treated, including those
deemed to be resistant. For practical purposes, a better
indicator of resistance is the minimum concentration that will
kill the bacteria treated (MBC), which is closer to the real,
in-use values.

Commercial products usually contain many ingredients in
addition to triclosan, but
laboratory studies usually dissolve triclosan in a single
solvent. Therefore, it is difficult to make general conclusions
since the effects of the
biocide depend on the
specific product involved and little is known about how
different chemicals might act when combined.

There are studies which expose
bacteria to low
concentrations of a
biocide and measure
how bacterial growth
changes with time. This is useful to determine changes in the
characteristics of the bacteria that survive the biocide, but it
does not tell whether or not bacteria will become
resistant to the
biocide and cross-resistant to unrelated compounds.

The methods used to determine
antibioticresistance are many and
varied and this has lead to contradicting results. There are no
standardised protocols that measure whether or not a
biocide can lead to
antibiotic-resistantbacteria, either because
the bacteria become resistant or because the non-resistant
bacteria are wiped out so that only the resistant or
insusceptible strains survive.

It would be useful to develop tools to define the minimum
concentration of a biocide
that will select or trigger the emergence of a mechanism that
will make bacteriaantibioticresistant. It would also
be useful to link the specific
genetic profile of
bacteria with the
resistance mechanism that
they are likely to develop. Using modern genetic methods it may
even be possible to develop routine tests that would identify
bacteria with resistance mechanisms.
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